Drug delivery systems for the treatment of disease or prophylactic vaccination for the prevention of disease which introduce active ingredients into the body are numerous and include oral, intranasal, transdermal, subcutaneous, intramuscular and intravenous administration. While these systems have been used for quite a long time and can deliver sufficient medication for the treatment or prevention of many diseases, there are numerous challenges associated with these drug delivery mechanisms, in particular, delivery of biological active agents or immunogenic compositions that should be able to elicit a protective immune response. Delivery of effective amounts of proteins, peptides and nucleic acids to prevent or treat a target disease has been problematic. Many factors are involved in introducing the right amount of the active agent in an appropriate drug composition or vaccine delivery system so that the formulation used contains the proper amount of active agent that can reach its target site(s) of action in order to attain a prophylactic or therapeutically effective response.
Vaccines are the most efficient and cost-effective means for disease prevention and treatment, however they comprise biological active agents which can require special manufacturing and storage conditions. Most vaccines are injectable and either provided in liquid form, or as a powder formulation which is reconstituted with a liquid prior to immunization. Injectable (intradermal, subcutaneous, intramuscular, intraperitoneal, etc.) vaccines can elicit systemic immune responses effectively. In certain cases, local immune responses to the injection are produced as side effects such as secretory immunoglobulin A (IgA or S-IgA) production at the injection site that can reduce the magnitude of the expected/desired target systemic effects, which in turn, does not consistently translate to systemic immunity. Local immune reactions to the injection can also lead to uncomfortable irritation, itching, and swelling. In some situations, booster or repeated injections of the vaccine are required to attain effective immunization as well as co administered adjuvants.
Liquid vaccine formulations often require cold-chain storage and transport to maintain biological activity, potency and therapeutic effectiveness prior to administration, and can also require a trained healthcare professional for their administration, and proper disposal of needle and syringe. Further, the individual being vaccinated may be obliged to visit a clinic or the office of the professional provider. These limitations make immunization campaigns difficult, particularly during a pandemic situation, an intentional release of an infectious agent or in geographic locations where infrastructure for vaccine storage, distribution and delivery is deficient or non-existent.
Thus uninterrupted maintenance of low temperatures within a specified range during storage and transport of vaccines is required to ensure preservation of biological activity and potency. Disruption of the cold chain system may diminish or completely eliminate vaccine efficacy underlying the importance of a fully functional cold chain network while bringing vaccine from producers to immunization sites to preserving product efficacy. Operating and maintaining an effective cold chain network is expensive and susceptible to interruptions, particularly in under-developed regions. In addition, conflict areas and certain developing countries often lack the infrastructure required for a cold chain system. The need of a refrigerated system poses a serious burden for delivering vaccine in conflict zones, developing countries and in emergency situations.
To overcome the limitations of existing injected vaccines, alternative vaccination strategies, for example, mucosal vaccination systems have been evaluated. Mucosal-associated lymphoid tissues (MALT) form the largest mammalian lymphoid organ system, contributing almost 80% of all immunocytes. Mucosal immunization not only induces systemic immunity (IgG and long lasting cell mediated immune response), but also induces local (s-IgA) immunity at the site of mucosal entry (common mucosal immune response). This common mucosal immune system is associated with organ selectivity demonstrated as enhanced memory at the site of mucosal priming. In addition, mucosal delivery is needle-free and painless, so it is likely to improve patient acceptance and is suitable for mass vaccination campaigns. FLUMIST® is an example of a Food and Drug Administration (FDA)-approved intranasal mucosal vaccine for immunizing against the influenza virus which uses a cold-adapted and temperature sensitive live virus as vaccine.
As mentioned above, current methods of manufacturing, transporting/storing and delivering vaccines prior to immunization is burdened by two major factors; 1) the vaccine must be maintained refrigerated prior to immunization and 2) gathering people for mass immunization. In some situations, these factors are critical and create extraordinary situations, including during outbreaks of pandemic influenza such as the 1918 flu (Spanish flu), and influenza A virus subtype H5N1, also known as “bird flu” and the H1N1 also known as “Swine flu.”
Pulmonary immunization against airborne pathogens in some cases has been shown useful, because the lungs contain a highly responsive immune system. The utility, effectiveness, and safety of pulmonary vaccination are well established for some agents such as the measles virus with the pioneering studies of Sabin in the early 1980s, and more recently with the mass vaccination campaigns in Mexico and South Africa. Published studies of inhaled vaccines for measles, influenza, and TB, however, have mostly involved nebulization of solutions, a method of administration that can be plagued by poor efficiency, lengthy administration time, and complex equipment. Accordingly, there is a need to develop new compositions and methods for immunizing against diseases, in particular, infectious and pandemic diseases which would provide a stable composition with a prolonged shelf-life in an easy to administer form and dispenser.